One of the major health needs in the elderly is to strengthen bone and prevent bone mass. In this project, we propose to investigate a novel mechanical loading model- knee joint loading - to stimulate bone formation and to strengthen mechanical properties of femur and a femoral neck. In our preliminary studies using mouse ulnae, bone formation was stimulated by loading an elbow joint. Furthermore, the loads required to induce bone formation with this elbow-loading model were smaller than that with a traditional longitudinal ulna-loading model. These results suggest that femur and a femoral neck can be strengthened by mechanical loads that are applied to a knee joint. The specific goal of the proposed project is to evaluate the effects of loads applied to the knee joint on bone mass and mechanical strength of femur and a femoral neck. The hypothesis, tested in the proposed study, is: "Low-amplitude sinusoidal mechanical loads with < 1 N at -20 Hz on a knee joint will stimulate new bone formation in femur and a femoral neck, and increase resistance to fracture." In the proposed study we will first identify the appropriate knee-loading conditions by examining streaming potentials and dissipation energy. Mechanical loads at physiological frequencies will be applied to the knee joint and streaming potentials and dissipation energy will be determined in the femur. Using the conditions that induce streaming potentials and elevate dissipation energy, we will then evaluate the loading effects through bone histomorphometry, micro-Computed Tomography (mu CT), and biomechanical tests. C57BL/6 mice will be given mechanical loads for 3 min per day for 3 consecutive days. After staining newly formed bone with calcein, bone morphometric parameters will be determined along a femoral midshaft. Three-dimensional morphology will be determined with mu CT, and mechanical parameters such as ultimate force, and work to failure will be determined. The proposed study will contribute to development of a novel loading model to strengthen bone without causing deformation of fragile bone in the elderly.